Therapeutic compounds

Patent metadata

Field	Value
Publication number	US-9879023-B2
Application number	US-201615257482-A
Country	US
Kind code	B2
Filing date	Sep 6, 2016
Priority date	Apr 21, 2011
Publication date	Jan 30, 2018
Grant date	Jan 30, 2018

Abstract

The invention provides compounds of formula I:

or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS or ARC symptoms in a mammal using compounds of formula I.

First claim

What is claimed is:

1. A compound, or pharmaceutically acceptable salt thereof, of formula Ia:

wherein:
R 1 is R 1a or R 1b ;
R 5 is R 5a or R 5b ;
R 1a is:
a) halo; or
b) H;

R 1b is cyano;
R 2 is (C 1 -C 6 )alkyl;
R 3 is —O(C 1 -C 6 )alkyl,
R 3′ is H;
R 4 is:

R 5a is:
a) H, (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heterocycle, heteroaryl, —C(═O)—R 11 , —C(═O)—O—R 11 , —O—R 11 or —(C 1 -C 6 )alkyl-R 11 ,
wherein each R 11 is independently H, (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heterocycle or heteroaryl, and wherein (C 6 -C 20 )aryl, heterocycle and heteroaryl are each optionally substituted with 1 to 3 Z 11 groups; or
b) —N(R 9 )R 10 or —C(═O)—N(R 9 )R 10 ,
wherein each R 9 is independently H or (C 1 -C 6 )alkyl
wherein each R 10 is independently H, (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, (C 6 -C 20 )aryl, heterocycle, —(C 1 -C 6 )alkyl-R 11 , or —C(═O)—R 11 , and wherein each R 11 is independently H, (C 1 -C 6 )alkyl, ((C 3 -C 7 )cycloalkyl, (C 6 -C 20 )aryl or heterocycle;

R 5b is:
a) —(C 2 -C 6 )alkynyl-(C 3 -C 7 )carbocycle; or
b) —NR e R f ;

each Z 11 is independently halo, (C 1 -C 6 )haloalkyl, —O(C 1 -C 6 )alkyl, —SO(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl, (C 6 -C 20 )aryl, heterocycle or heteroaryl, wherein (C 6 -C 20 )aryl, heterocycle and heteroaryl are each optionally substituted with halo, (C 1 -C 6 )alkyl or COOH;
each R e is independently (C 1 -C 6 )alkyl;
each R f is independently —(C 1 -C 6 )alkyl-Z 6 ;
each Z 6 is independently —NR a R a or —C(O)NR c R d ;
each R a is independently (C 1 -C 6 )alkyl; and
R c and R d are each independently (C 1 -C 6 )alkyl;
wherein each heteroaryl has 1 to 6 carbon atoms and 1 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, and each heterocycle has 1 to 6 carbon atoms and 1 to 3 heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein
R 5a is H, (C 1 -C 6 )alkyl, (C 3 -C 7 )carbocycle, —(C 1 -C 6 )alkyl-R 11 , —C(═O)—R 11 , —N(R 9 )R 10 , —C(═O)—N(R 9 )R 10 , heterocycle or heteroaryl,
wherein heterocycle or heteroaryl is optionally substituted with 1 to 3 Z 11 groups, and
wherein R 5b is —(C 2 -C 6 )alkynyl-(C 3 -C 7 )carbocycle.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein
R 5 is H, (C 1 -C 6 )alkyl, (C 3 -C 7 )carbocycle, —(C 1 -C 6 )alkyl-R 11 , —C(═O)—R 11 , —N(R 9 )R 10 , —C(═O)—N(R 9 )R 10 , heterocycle or heteroaryl,
wherein heterocycle or heteroaryl is optionally substituted with 1 to 3 Z 11 groups.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is —OC(CH 3 ) 3 .

5. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

6. A method of treating HIV infection in a patient in need thereof comprising administering a compound as described in claim 1 , or pharmaceutically acceptable salt thereof, to the patient.

7. A method for treating an HIV infection in a patient in need thereof comprising administering to the patient a compound as described in claim 1 , or a pharmaceutically acceptable salt thereof, in combination with one or more additional therapeutic agents selected from the group consisting of HIV protease inhibiting compounds, HIV non-nucleoside inhibitors of reverse transcriptase, HIV nucleoside inhibitors of reverse transcriptase, HIV nucleotide inhibitors of reverse transcriptase, HIV integrase inhibitors, gp41 inhibitors, CXCR4 inhibitors, gp120 inhibitors, CCR5 inhibitors, capsid polymerization inhibitors, and other drugs for treating HIV, and combinations thereof.

Assignees

• Gilead Sciences Inc

Inventors

• Babaoglu Kerim
• Mitchell Michael L
• Mcfadden Ryan
• Roethle Paul A
• Xu Lianhong
• Yang Hong

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/18

  for HIV · CPC title

• C07D277/82

  Nitrogen atoms · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07D277/62 Primary

  Benzothiazoles · CPC title